Class II HMG-COA reductase inhibitors and methods of use

Abstract

Disclosed are compositions and methods for treating bacterial infections.

It is claimed: 
     
       1. An inhibitor of Class II 3-hydroxy-3-methylglutaryl-coenzyme A reductase having one of the following structures: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 =is a hydroxyl; 
         R 2 =is H; 
         D is CR 4 , wherein R 4  is (CH 2 ) 4 CH(CH 3 ) 2 , (CH 2 ) 3 CH(CH 3 ) 2 , (CH 2 ) 2 C(CH 3 ) 3  cyclohexylethyl, or (CH 2 ) m R c , wherein m=6-14 and R C =H; 
         R 5 =H; 
         A, B, E, X, Y, and Z are each CH; 
         or a pharmaceutically acceptable salts thereof. 
       
     
     
       2. The inhibitor of  claim 1  selected from 5-[N-(4-decylphenl)sulfamoyl]-2-hydroxybenzoic acid, 5-[N-(4-cyclohexylethylphenyl)sulfamoyl]-2-hydroxybenzoic acid, 2-hydroxy-5-[N-(4-(5-methylhexyl)phenyl)sulfamoyl]benzoic acid, 5-[N-(4-heptylphenyl)sulfamoyl]-2-hydroxybenzoic acid and pharmaceutically acceptable salts thereof. 
     
     
       3. An inhibitor according to  claim 1 , the inhibitor having antimicrobial activity against one or more bacterial or fungal pathogens. 
     
     
       4. The inhibitor of  claim 1 , wherein the bacterial pathogen is a Gram-positive pathogen. 
     
     
       5. The inhibitor of  claim 3 , wherein the pathogen is selected from the group consisting of  Bacillus anthracis, Bacillus subtilis, Bacillus cereus, Listeria monocytogenes, Brucella abortus, Candida albicans, Staphylococcus aureus, Enterococcus faecalis  and  Streptococcus pneumoniae.    
     
     
       6. The inhibitor according to  claim 3 , wherein the pathogen is resistant to vancomycin and/or methicillin. 
     
     
       7. An inhibitor according to  claim 1 , wherein the inhibitor exhibits no toxicity or low toxicity toward mammalian cells. 
     
     
       8. An pharmaceutical composition comprising:
 a pharmaceutically acceptable excipient; and 
 a compound according to  claim 1 . 
 
     
     
       9. A method of treating a multicellular organism infected with a bacterial or fungal pathogen comprising administering to the organism the pharmaceutical composition of  claim 8  in an amount effective to kill or inhibit growth of the pathogen. 
     
     
       10. The method of  claim 9 , wherein the organism is a human. 
     
     
       11. A biocide comprising:
 a diluent; and 
 a compound according to  claim 1 . 
 
     
     
       12. A method of disinfecting a surface comprising or at risk for comprising planktonic or adherent pathogenic bacteria comprising contacting the surface with an effective amount of the biocide of  claim 11  for a period of time sufficient to kill or inhibit growth of the bacteria.